Cutaneous Leishmaniasis in North-Central Ethiopia: Trend, Clinical Forms, Geographic Distribution, and Determinants Belayneh Eshetu1 and Hassen Mamo2*

Eshetu and Mamo Tropical Medicine and Health (2020) 48:39 Tropical Medicine https://doi.org/10.1186/s41182-020-00231-w and Health

RESEARCH Open Access Cutaneous leishmaniasis in north-central Ethiopia: trend, clinical forms, geographic distribution, and determinants Belayneh Eshetu1 and Hassen Mamo2*

Abstract Background: Cutaneous leishmaniasis (CL), being among the neglected tropical diseases, catches little attention despite its considerable influence. This study aimed at estimating the prevalence and associated factors of CL in Boru Meda Hospital, Dessie town, north-central Ethiopia. Methods: Medical records of patients who attended the Dermatology Department of the Hospital in 2012–May 2018 were assessed. In addition, dermatological patients who were visiting the hospital during the data collection period (November 2017–May 2018) were interviewed to capture socio-demographic, environmental variables, and related factors. The source population was individuals who visited the hospital for skin problems in the stated years and CL positives were the targets. The association between CL and its determinants was tested by logistic regression. Results: CL prevalence was 1.5% showing increasing trend with the year of examination. Localized, diffused, and mucosal CL was evident across the years. Dessie town had the highest prevalence, 291 (32.8%) patients out of 888 cases. The number of examined (29,701) and positives (543, 1.8%) for males was comparable with females, 28,459 and 345 (1.2%), respectively, increasing with age but without significant difference. Dessie town residence (adjusted odds ratio (AOR) 12.2, 95% confidence interval (CI) 2.2–18.6, p = 0.01), no bed net (AOR 9.9, 95% CI 2.7–16.7, p < 0.01), nearby irrigation (AOR 8.1, 95% CI 1.9–12.4, p < 0.01), and travel to CL endemic areas (AOR 13.9, 95% CI 4.4– 14.3, p < 0.01) were significantly associated with CL. Conclusion: CL is a growing health problem in Dessie and its surroundings. Known risk factors prevail. Comprehensive parasitological, entomological, and social studies are warranted to better manage the disease. Keywords: Cutaneous leishmaniasis, Prevalence, Determinants, Adjusted odds ratio, Dermatology

Introduction cutaneous lesions or nodules termed cutaneous leish- Leishmaniasis is a collective name of diseases caused by maniasis (CL) to a fatal systemic illness called visceral different species of the intracellular protozoa of the leishmaniasis (VL) or more commonly kala-azar. In be- genus Leishmania [1] and transmitted by the bite of fe- tween, there is mucocutaneous leishmaniasis (MCL) or male phlebotomine sandflies of the genera Phlebotomus “espundia” and post-kala-azar dermal leishmaniasis— or Lutzomyia [2]. Human leishmaniasis is manifested in PKADL [3]. MCL, which is primarily caused by Leish- distinct clinical forms ranging from mild self-healing mania braziliensis braziliensis and most commonly existing in Bolivia, Brazil, and Peru, affects the mucosa * Correspondence: [email protected] membrane and if untreated may be fatal invariably [4]. 2Department of Microbial, Cellular and Molecular Biology, College of Natural VL caused by L. donovani complex is a febrile malaria- and Computational Sciences, Addis Ababa University, PO Box 1176, Addis resembling illness characterized by swelling of the lymph Ababa, Ethiopia Full list of author information is available at the end of the article nodes, the liver, and spleen (hepatosplenomegaly) and

© The Author(s). 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. Eshetu and Mamo Tropical Medicine and Health (2020) 48:39 Page 2 of 10

anemia, emaciation, and eventually death in the absence aethiopica [35] though there were some cases by L. of intervention [5]. VL is a widely distributed tropical major and L. tropica [36]. and subtropical disease occurring in almost all conti- Several people from Dessie town, north-central nents with the possible exception of Australia although Ethiopia, and the surrounding areas visit Boru Meda the highest burden is borne in Bangladesh, Brazil, India, Hospital (BMH) for skin diseases of multiple etiologies Nepal, and Sudan [6]. including CL. Furthermore, people with cured scars or However, CL is by far the most common form of leish- active CL lesions are visible in schools, on the street, maniasis mainly caused by L. major, L. tropica, and L. markets, and other places in the town. However, there is aethiopica in Europe (the Mediterranean basin), Asia no recent information on the magnitude of CL in and (the Middle East and Central Asia) and Africa, and L. around Dessie, except an attempt on the treatment effi- mexicana in the Americas. In Asia, CL is predominantly cacy of anti-leishmaniasis agents on a limited number of found in Afghanistan, Iran, Saudi Arabia, and Syria; in patients (n = 97) in BMH [34]. This study was aimed at Africa, in Algeria, and in South America Brazil, assessing the prevalence of CL among the patients at- Colombia and Peru take the biggest share. About 95% of tending BMH and the associated risk factors. Medical CL cases with over two thirds of new CL cases occur in reports, combined with future field works and molecular these countries [7]. Overall, CL is currently endemic in analyses as well as entomological surveys will help iden- 88 countries globally (20 countries in South and Central tify the status of local transmission of CL and its spatial America and 68 in Europe, Africa, the Middle East, Cen- and temporal distribution. Such an investigation will tral Asia, and the Indian subcontinent). An estimated provide better insights into the problem and contribute 700,000 to 1,000,000 new cases and some 26,000 to 65, towards designing sustainable CL management strategies 000 deaths occur annually, but only 19–37% is actually in Dessie and its environs. reported to health authorities although there are an estimated 12 million cases worldwide [7]. Methods Although leishmaniasis is considered the sixth most The study area significant disease in the tropics/subtropics by the World The study area is Dessie town in north-central Ethiopia Health Organization (WHO), CL remains among the some 388 km from Addis Ababa with latitude and longi- neglected tropical diseases (NTDs) [8]. As CL leaves a tude of 11° 8′ N 39° 38′ E and 2470–2550 m above sea disfiguring scar on the patient’s body, it is a cause of life- level. Dessie was established by King Michael in 1893 long stigma and discrimination leading to significant currently covering an area of 16000 ha. It is divided into psychosocial problems [9, 10]. Currently, the incidence 10 sub-cities and 6 rural kebeles (the lowest administra- of CL is growing and projected to be more in the future tive unit). The study was conducted in BMH. According for factors related to poverty and its various manifesta- to the information obtained from the Hospital, BMH tions [11], climatic/environmental changes [12], drug- was established in 1955 by the Sudan Interior Mission resistance [13], exoduses because of conflicts [14, 15], (SIM). During its establishment, it was intended that the and immunodeficiency particularly due to AIDS [16]. hospital would provide ophthalmological and dermato- Since its first description by the Italian epidemiologist logical services. After serving for about 40 years as per Martoglio in 1913 [17], several authors in the late 1960s its initial objective, the hospital was upgraded to deliver and early 70s (Balzer et al. 1960 (in [18–20])) reported comprehensive medical services now. Around 2.5 million the occurrence of CL in a number of localities in people living in South and North Wollo Zones, Oromia Ethiopia and described its epidemiology. Subsequent Special Zone, North Shewa, South Tigray, and parts of surveys further established the endemicity of CL in most Afar Region are served by the hospital. The hospital highlands of Ethiopia with preponderance in areas remained the only well-recognized center for skin 1400–2700 m above sea level. To mention a few, wide disease management in the eastern part of the Amhara CL foci occur in different parts of Tigray [21–24] and Region and beyond. Gondar [25] in the north and northwest, Dembidolo (Wollega) in the west [26], Silti [27], Sidamo [28] and Study design, population, and data collection Ocholo (Gamo Gofa) in the south [29–31], and Addis Patients who presented to BMH Dermatology Department Ababa and its surroundings in the center [32, 33]. CL between October 2017 and May 2018 were recruited and has different vernacular names in different localities of interviewed to gather important socio-demographic and Ethiopia like bolbo in Ocholo, finchottu in Central Shoa, other related information, and their CL status was deter- shahegne in North Shoa, kunchir in Gojam, Gondar and mined clinically and/or parasitologically (Giemsa stains of parts of Wollo, giziwa in Tigray, chewie in Sodo, and skin slit smear or fine-needle aspiration cytology (FNAC)/ simbirahalkm in Wollega as reviewed in Seife et al. 2018 skin biopsy) as well as culture. The questionnaire was [34]. The majority of CL cases in Ethiopia are due to L. adopted from the literature and used with slight Eshetu and Mamo Tropical Medicine and Health (2020) 48:39 Page 3 of 10

modification. The original English version of the question- of females in 2016 and 2017. Among the CL positives (n naire was translated first into Amharic and back into Eng- = 888), 543(61.1%) were males and 345(38.9%) females. lish to assure consistency. Then, it was administered to There was a slightly higher prevalence of CL positivity in patients who came to the hospital for CL and other skin males than in females in all the years considered al- disease treatment. The collected data were checked for though the difference was not statistically significant. completeness, accuracy, clarity, and consistency. Addition- The proportion of CL-positive individuals was differ- ally, the medical records of individuals who visited the ent in different age groups for both genders. In general, hospital in the preceding years (January 2012–September there was an increasing trend of CL cases with age and 2017) for the same problem were considered and CL- in both genders; those over 14 years were the most af- positive cases (clinical/parasitological/culture) identified fected. While 3.4%, 11.6%, and 46.2% of under-5, 5–14 and socio-demographic data extracted. and > 14-year-old males were CL-positive, the corre- sponding proportions of females were 2.7%, 9.5%, and Data analysis 26.7% (Table 2). While the dependent variable was CL positivity, the in- dependent variables constituted socio-demographics Patient place of residence such as age, sex, knowledge, residence area, and related The CL cases in the Hospital were from about thirty- household and environmental factors. The differences three districts including Dessie town. Nineteen of these between age and gender categories as well as residence, are South Wollo Zone districts; all the districts in the which were the only available variables for the retro- Zone had CL cases. The remaining thirteen are from spective data, with regard to CL have been tested by the North Wollo (9), North Shoa (2), and Oromia Special chi-square test. Univariable and multivariable logistic re- Zone (2) which share borders with South Wollo. One gression tests at 95% confidence intervals (CI) were used district having three CL cases belongs to Tigray Region to assess the association between the dependent and in- and is located at North Wollo boundary. Quantitatively, dependent variables for the interviewed patients only. 789 (89.0%) of the CL cases were from South Wollo, 74 Statistical significance was at p < 0.05. The statistical (8.0%) from North Wollo, 13 (2.0%) North Shewa, and 9 analysis was carried out using the Statistical Package for (1.0%) from Oromia. The proportion of CL cases from Social Sciences (SPSS IBM Statistics) version 20. Dessie town was the highest (291 (33.0%) followed by Kutaber (183 (21.0%) and Tehulederie (72 (8.0%) that Results are within the immediate vicinity (Fig. 1). CL cases by age and gender In the past six and half year (January 2012–May 2018), Repeated and new CL cases, type, and location of lesion totally 58,163 people were examined in the Dermatology Among patients of CL who were examined in the Hos- Department of BMH. Of these, 29,704 were males and pital, 521(58.7%) were new cases – 318 (58.6%) males 28,459 females (male to female ratio nearly 1:1). The and 203 (58.8%) females. The rest 367(41.3%) were pre- total prevalence of CL was 1.5% with 543 (1.8%) males viously treated cases. That is, males and females who and 345 (1.2%) females (Table 1). The rate of CL in- took treatment more than once in the Hospital for CL creased from 0.9% in 2012 to 3.5% in 2018. Overall as were respectively 225 (61.3%) and 142 (38.7%). The well as throughout, slightly more males were examined number and proportion of newly (once) and repeatedly for skin problems except for the slightly higher number treated (relapse) individuals in the hospital had shown

Table 1 Prevalence of CL among patients who visited the BMH Dermatology Department from 2012 to 2018 Year Examined CL positive Male, n (%) Female, n (%) Total Male, n (%) Female, n (%) Total, n (%) 2012 2327 (53.6) 2016 (46.4) 4343 26 (1.1) 15 (0.7) 41 (0.9) 2013 3363 (51.8) 3129 (48.2) 6492 27 (0.8) 14 (0.5) 41 (0.6) 2014 3181 (54.6) 2644 (45.4) 5825 34 (1.1) 13 (0.5) 47 (0.8) 2015 4779 (53.8) 4102 (46.2) 8881 29 (0.6) 23 (0.6) 52 (0.6) 2016 4664 (49.9) 4683 (50.1) 9347 38 (0.8) 30 (0.6) 68 (0.7) 2017 7507 (48.4) 8014 (51.6) 15,521 221 (2.9) 149 (1.9) 370 (2.4) 2018* 3883 (50.1) 3871 (49.9) 7,754 168 (4.3) 101 (2.6) 269 (3.5) Total 29,704 (51.1) 28,459 (48.9) 58,163 543 (1.8) 345 (1.2) 888 (1.5) BMH Boru Meda Hospital, CL cutaneous leishmaniasis, n number, % per cent *2018 data was only up to May Eshetu and Mamo Tropical Medicine and Health (2020) 48:39 Page 4 of 10

Table 2 CL in different age and sex groups among patients who visited the BMH Dermatology Department between 2012 and May 2018 (N = 888) Age Sex Year (year) 2012 2013 2014 2015 2016 2017 2018* Total n (%) n (%) n (%) n (%) n (%) n (%) n (%) n (%) < 5 Male 1 (3.3) 1 (1.3) 1 (1.3) 4 (13.3) 0 (0.0) 16 (53.3) 7 (23.3) 30 (3.4) Female 0 (0.0) 1 (4.2) 0 (0.0) 1 (4.2) 3 (12.5) 12 (50.0) 7 (27.2) 24 (2.7) Total 1 (1.9) 2 (3.7) 1 (4.2) 5 (9.3) 3 (5.7) 28 (51.9) 14 (25.9) 54 (6.1) 5–14 Male 7 (6.8) 6 (5.8) 6 (5.8) 4 (3.9) 7 (6.8) 47 (45.6) 26 (25.2) 103 (11.6) Female 2 (2.4) 2 (2.4) 4 (4.8) 5 (5.9) 7 (8.3) 45 (53.6) 19 (22.6) 84 (9.5) Total 9 (4.8) 8 (4.3) 10 (5.4) 9 (4.8) 14 (7.5) 92 (49.2) 45 (24.1) 187 (21.1) > 14 Male 18 (4.4) 20 (10.7) 27 (6.6) 21 (5.1) 31 (7.6) 159 (38.8) 134 (32.7) 410 (46.2) Female 13 (5.5) 11 (4.6) 9 (3.8) 17 (7.2) 20 (8.4) 92 (38.8) 75 (31.7) 237 (26.7) Total 31 (4.8) 31 (4.8) 36 (5.6) 38 (5.9) 51 (7.9) 251 (38.8) 209 (33.3) 647 (72.9) Overall Male 26 (4.8) 27 (4.9) 34 (6.3) 29 (5.3) 38 (6.9) 221 (40.7) 168 (30.9) 543 (61.2) Female 15 (4.4) 14 (4.1) 13 (3.8) 23 (6.7) 30 (8.7) 149 (43.2) 101 (29.3) 345 (38.9) Total 41 (4.6) 41 (4.6) 47 (5.3) 52 (5.9) 68 (7.7) 370 (41.7) 269 (30.3) 888 (100) BMH Boru Meda Hospital, CL cutaneous leishmaniasis, n number, % percent *2018 data was only up to May variation with the year of examination. Specifically, available within patient medical records. Similarly, data 68.3%, 75.6%, 74.1%, 71.5%, 80.9%, 54.9%, and 49.1% for the four different diagnostics (clinical, skin slit smear, attended treatment once and 31.7%, 24.4%, 25.5%, 28.9%, FNAC, and culture) that are reported practiced in the 19.1%, 45.1%, and 50.9% treated more than once during hospital were not available. the study period from 2012 to May 2018, respectively. The data showed that more repeat-cases were observed Questionnaire data in 2017 and 2018 than the rest of the years (Table 3). The questionnaire data showed that out of 354 respon- Out of the 888 patients, 792 (89.2%) were localized cu- dents, 216 (61.0%) were males and 138 (38.9%) females. taneous leishmaniasis (LCL), 35 (3.9%) diffuse cutaneous Twenty-four (6.8%) of the respondents were under-5 leishmaniasis (DCL) and 61(6.9%) were MCL cases. The children, 52 (14.7%) 5–14 years and the rest 278 (78.5%) data showed that the majority of the cases were local- over 14 years. Most (141) of the respondents were sec- ized, particularly at the nose and cheek. The duration of ondary school students, 89 at primary school, 72 joined lesions, treatment, and treatment outcomes was not college and university education, and the rest 52 had no

Fig. 1 Map of Ethiopia, Amhara Region, and South Wollo Zone Districts where from cutaneous leishmaniasis (CL) patients of Boru Meda Hospital originated. The figure inside each district indicates the number of CL cases. Since Dessie town and Kutaber are closer to the Hospital, more people are expected to be examined and correspondingly more are CL-positive. So, unless the number of people examined is known it may be misleading to conclude that the highest number and proportion of CL were from these districts Eshetu and Mamo Tropical Medicine and Health (2020) 48:39 Page 5 of 10

Table 3 New and repeat CL cases among patients who were treated at the BMH Dermatology Department from 2012 to May 2018 CL Year of examination cases 2012 2013 2014 2015 2016 2017 2018 Total Overall MF MF MF MF MF M F M F M F Repeat 8573931057690779443225142367 New 18 10 20 11 25 10 19 18 31 24 131 72 74 58 318 203 521 Total 26 15 27 14 34 13 29 23 38 30 221 149 168 101 543 345 888 CL cutaneous leishmaniasis, F female, M male formal schooling. Hundred seventy-nine of the respon- 2018 was 1.5%. This is much lower than the prevalence dents (50.6%) were CL-positive (111 males and 68 reported by similar health facility-based studies in females). Most (76 or 42.5%) of the CL-positive individ- Ethiopia such as Addis Ababa 14.2% [33]. Although the uals were secondary school students, 34 (19.0%) without nationwide prevalence of CL is lacking in Ethiopia, there schooling, 45 (25.1%) primary school attending, and the are some community-based cross-sectional surveys rest 24 (13.4%) had tertiary education. showing 2.3–14.0% prevalence [15, 23, 24, 27] from vari- Out of 197 (55.7%) students, 54 (15.3%) farmers, 52 ous parts demonstrating remarkable heterogeneity. A (14.7%) civil servants, and 51 (14.4%) merchants; CL- meta-analysis and systemic review [37] reported a positive individuals were 103 (55.5%), 37 (20.7%), 17 pooled prevalence of 19.0%. The relatively lower preva- (9.5%), and 22 (12.3%), respectively. From student re- lence of CL in the study area might be due to a number spondents 52.3% individuals, among farmer participants of reasons. Previously, some people might follow trad- 68.5%, from merchants 43.1%, and from the governmen- itional medication options. Others used to visit the hos- tally employed respondents 32.7% were CL-positive pa- pital, diagnosed but referred to other hospitals where tients. The data showed that CL cases were greatest in leishmaniasis treatment service is readily available. How- farmers and least among civil servants. ever, recently, the hospital has started serving CL pa- Only 83 respondents knew what CL meant and 34 had tients as any other skin disease cases (personal knowledge about its transmission. Among the respon- communication, hospital staff). During the time of the dents, 116 (32.8%) responded their living houses were study, several people were attending the hospital for CL built from muddy and grassy materials and 183 (51.7%) treatment from different nearby as well as distant areas. were living in houses with cracked walls and only The increased prevalence of CL cases in 2017 and up to 53(14.9%) lived in houses with moist floors. Concerning May 2018 corroborates this explanation. The CL preva- sleeping outside under a tree, only 36 (10.2%) agreed lence increased from 0.9% in 2012 to 3.5% in 2018 to that they sleep outside under trees. However, 318 May. (89.8%) people sleep inside. Only 27 (7.6%) of the re- The percentage of CL-positive males was 1.8% which spondents responded that they use bed nets. There were was comparable with females (1.2%) agreeing with a re- dogs and other animals like cattle in the houses of 248 port from different localities of Ethiopia at different (70.1%) of the respondents. Ninety-three (26.3%) were times [19, 24, 30], and in some countries like Saudi Ara- living near irrigation areas, 54 (15.3%) near open sewage bia in the Middle East [38] where no significant gender areas, and 54 (15.3%) had traveled to CL endemic areas. disparity was recorded. Further, a study in Argentina Among the variables tested in the univariate analysis from South America [39] reported no significant differ- most were significantly associated with CL positivity ex- ence between males and females suggesting equal expos- cept gender, age, sleeping under the tree, and being a ure to infection. merchant or living outside Dessie town or Kutaber On the other hand, a number of findings indicated (Table 4). that the male gender is a risk factor for CL in different In the multivariable model, Dessie town residence, lack countries (reviewed in ref no. [38, 40], and [41] including of CL knowledge, living in muddy and grassy houses or Ethiopia [22]). The authors attribute this to variations in cracked-wall houses, lack of bed net, irrigation nearby, the activities of males and females and thus exposure to possession of dogs or other animals, and travel history the sandfly vectors, provided there is no significant dif- to CL endemic areas were significantly associated with ference in gender attendance to health services. Males CL occurrence (Table 5). may have closer contact with the habitat of the sandfly through occupation and leisure activity. Cultural activ- Discussion ities that mostly males are faced with outdoor activities The overall prevalence of CL among patients who visited including farming, keeping cattle, staying around gorges, the BMH Dermatology Department from 2012 to May and/or farmland for a long period and the presence of Eshetu and Mamo Tropical Medicine and Health (2020) 48:39 Page 6 of 10

Table 4 Univariable logistic regression analysis of potential determinants in relation to CL positivity at BMH, Dessie town, Northeast Ethiopia, November 2017–May 2018 (N = 354) Variable Alternatives N Pos (%) COR 95% CI P value Gender Male 216 111 (51.4) 0.9 0.6-1.4 0.69 Female 138 68 (49.3) 1.0 –– Age (year) < 5 24 3 (12.5) 1.0 –– 5–14 52 16 (30.8) 1.2 0.6–2.1 0.62 > 14 278 160 (57.6) 1.5 0.9–2.6 0.07 Residence Dessie town 137 80 (58.4) 3.9 1.2–12.7 0.02 Kutaber 79 46 (58.2) 3.8 1.1–13.1 0.03 Tehulederie 34 17 (50.0) 2.8 0.7–10.3 0.13 Other South Wollo areas 17 9 (52.9) 3.1 0.7–13.7 0.13 Delanta 23 9 (39.1) 1.8 0.4–7.2 0.43 Ambasel 18 7 (38.9) 1.8 0.4–7.7 0.46 Dessie Zuria 19 5 (26.3) 0.9 0.2–4.6 0.98 South Wollo border areas 15 4 (26.7) 0.6 0.1–3.7 0.53 Kalu 12 2 (16.7) 1.0 –– Education No formal schooling 52 34 (65.4) 3.8 1.8–8.1 0.00 Primary school 89 45 (50.6) 2.0 1.1–3.9 0.02 Secondary school 141 76 (53.9) 2.3 1.3–4.2 0.00 Tertiary education 72 24 (33.3) 1.0 –– Job Civil servant 52 17 (32.7) 1.0 –– Farmer 54 37 (68.5) 4.5 1.9–10.1 < 0.01 Student 197 103 (52.3) 2.3 1.2–4.3 0.01 Merchant 51 22 (43.1) 1.6 0.7–3.5 0.27 Know what CL is Yes 83 27 (32.5) 1.0 –– No 271 152 (56.1) 2.6 1.6–4.4 < 0.01 Know CL transmission Yes 34 5 (14.7) 1.0 – No 320 174 (54.4) 6.9 2.6–18.3 < 0.01 Know factors related to CL Yes 32 5 (15.6) 1.0 – No 322 174 (54.0) 6.3 2.4–16.9 < 0.01 Muddy-grassy houses Yes 116 85 (73.3) 4.2 2.6–6.8 < 0.01 No 238 94 (39.5) 1.0 – Wall cracks Yes 183 122 (66.7) 3.9 2.5–6.0 < 0.01 No 171 57 (33.3) 1.0 – Moist floor Yes 53 36 (67.9) 2.8 1.3–4.3 0.00 No 301 143 (47.5) 1.0 – On-floor sleeping Yes 47 42 (89.4) 10.4 4.0–7.0 < 0.01 No 307 137 (44.6) 1.0 –– Bed net use Yes 27 4 (14.8) 1.0 –– No 327 175 (53.5) 6.6 2.2–9.6 0.01 Sleeping under tree Yes 36 23 (63.9) 1.8 0.9–3.8 0.09 No 318 156 (49.1) 1.0 –– Open sewage nearby house Yes 54 37 (67.5) 2.4 1.3–4.5 0.00 No 300 142 (47.3) 1.0 –– Irrigation nearby house Yes 93 84 (90.3) 16.3 7.8–13.9 < 0.01 Eshetu and Mamo Tropical Medicine and Health (2020) 48:39 Page 7 of 10

Table 4 Univariable logistic regression analysis of potential determinants in relation to CL positivity at BMH, Dessie town, Northeast Ethiopia, November 2017–May 2018 (N = 354) (Continued) Variable Alternatives N Pos (%) COR 95% CI P value No 261 95 (36.4) 1.0 –– Traveled to CL endemic areas Yes 54 46 (85.2) 7.2 3.3–15.8 < 0.01 No 300 133 (44.3) 1.0 –– Own dogs and other animals Yes 248 137 (55.4) 1.9 1.2–2.9 0.00 No 106 42 (39.6) 1.0 –– Note: n number, Pos positive, COR crude odds ratio, CI confidence interval, significant at p < 0.05 endemic sites that mostly males could travel there for the different districts. The data showed that the highest work. CL prevalence was in Dessie town. The high prevalence Furthermore, the gender difference in CL incidence is of CL in Dessie town and Kutaber district could be due attributable to sex hormonal effects or immune re- to the higher altitude of 2500 m above sea level together sponses [42], as it has been noted in some other parasitic with other factors such as recent urbanization, especially diseases [43]. Differences in exposure or access to in Dessie. CL is distributed mainly at high and mid alti- healthcare per se do not necessarily explain gender- tudes ranging from 1400 to 2700 m above sea level, based differences for infection or clinical disease. The which is most favorable for the proven vector sandfly role of gender in reference to infectious diseases is dem- species. In a recent mapping study in Ethiopia [46], CL onstrated in an animal model as well [44]. In general, occurrence was significantly associated with an altitud- there is a strong correlation between gender and inci- inal range between 810 and 3563 m above mean sea level dence of leishmaniasis and the disease is more frequent increasing slope values producing higher CL correla- among men than women although the current study did tions. The results show the widespread endemicity of CL not suggest that. in Dessie town and its surroundings calling for future The secondary data collected from the hospital records field-based epidemiological surveys. Previous reports showed that the total percentage of CL positive individ- concerning the endemicity of CL in Kutaber, which is uals was different between age groups. Out of 888 CL- some 10 km from Dessie town [18]and“Dessie area” positive individuals, 6.1%, 21.1%, and 72.9% were under- [19], exist, but this report is the first of its kind for CL 5, 5–14, and ≥ 15, respectively, although the number of from Dessie town proper in recent times. The examined in each group is unknown. The primary data urbanization process of the town, which is a well-known also revealed an almost similar pattern in relation to age risk factor for CL, is ongoing [47]. although in the logistic regression age was not identified The data showed that the CL prevalence was highest as a significant risk factor. This might be due to the out- for farmers (68.5%) and least among civil servants. Farm- door activities performed by individuals of this age ing activity could put farmers at greater risk of CL than group in farms and the likes than individuals below this non-farmers such as government employees. In the farm age as they are actively working groups. field and irrigation areas, and possible travel to endemic Nevertheless, the age-related pattern of CL attack is areas and other seasonal activities farmers could be variable across studies in Ethiopia. In some, the more more exposed to sandfly bites. Students are second in predominantly affected group is the younger 0–9[24], in CL prevalence because most students are families of others, the 11–20 [27], > 14 [22], or those 10–19 years farmers and engaged in similar activities as their parents. old [23]. The data showed that the majority (89.2%) of Lack of CL knowledge, living in houses constructed of the CL cases were localized, particularly at the nose and mud and grass, presence of cracks in house wall, sleep- cheek. Diffuse and mucocutaneous accounted only for ing on the floor, lack of using bed net during sleeping, 3.9% and 6.9%, respectively. It is known that sandfly vec- presence of plants and irrigation areas nearby houses, tors bite in the face, which is exposed, and cutaneous le- presence of dogs and other animals in the compound or sions appear in the site of promastigote inoculation living houses, and travel history to endemic areas are following the bite. In other localities and countries, the significantly associated with CL. The responses of the face is noticed as the most infected organ by the Leish- participants on the knowledge-based questionnaire mania although some other studies showed leishmania- showed that the majority of the respondents were not sis lesions in the hands and feet as well [45]. aware of the meaning, transmission, and associated risk The current hospital data indicates that CL cases were factors of CL, and this lack of knowledge was signifi- observed in 35 different districts including Dessie town. cantly associated with CL. This result is in agreement There was a greater variation of CL prevalence amongst with reports and reviews by various authors [48–51]. Eshetu and Mamo Tropical Medicine and Health (2020) 48:39 Page 8 of 10

Table 5 Multivariable logistic regression analysis result of risk factors for CL positivity at BMH, Dessie town, north-central Ethiopia, November 2017–May 2018 (N = 354) Variable Categories n Pos, n (%) AOR 95% CI P value Residence district Dessie town 137 80 (58.4) 12.2 2.2–18.6 0.00* Kutaber 79 46 (58.2) 11.6 0.9–16.2 0.06 Other South Wollo areas 17 9 (52.9) 11.6 0.8–17.4 0.07 Tehulederie 34 17 (50.0) 10.4 0.5–19.8 0.13 Delanta 23 9 (39.1) 10.2 0.5–18.5 0.13 Ambasel 18 7 (38.9) 6.9 0.5–10.3 0.15 South Wollo border areas 15 4 (26.7) 5.14 0.3–7.9 0.23 Dessie Zuria 19 5 (26.3) 2.2 0.1–6.5 0.62 Kalu 12 2 (16.7) 1.0 –– Education No formal schooling 52 34 (65.4) 4.4 0.8–5.1 0.093 Primary school 89 45 (50.6) 0.9 0.9–3.5 0.8 Secondary school 141 76 (53.9) 1.2 0.2–3.5 0.8 Tertiary 72 24 (33.3) 1.0 –– Job Civil servant 52 17 (32.7) 1.0 –– Merchant 51 22 (43.1) 2.3 0.4–15.6 0.33 Student 197 103 (52.3) 2.5 0.4–14.7 0.28 Farmer 54 37 (68.5) 3.1 0.5–11.4 0.31 Know what CL is Yes 83 27 (32.5) 1.0 –– No 271 152 (56.1) 3.9 1.3–11.4 0.01* Know CL transmission Yes 34 5 (14.7) 1.0 –– No 320 174 (54.9) 3.4 0.9–13.7 0.08 Know factors related to CL Yes 32 5 (15.6) 1.0 –– No 322 174 (54.0) 2.7 0.6–12.3 0.21 Muddy-grassy house Yes 116 85 (73.3) 4.2 1.7–10.5 0.00* No 238 94 (39.5) 1.0 –– House wall cracks Yes 183 122 (66.7) 3.2 1.4–7.0 0.00* No 171 57 (33.3) 1.0 – On-floor sleeping Yes 53 36 (67.9) 1.7 0.7–4.4 0.32 No 301 143 (47.5) 1.0 –– Bed net use Yes 27 4 (14.8) 1.0 –– No 327 175 (53.5) 9.9 2.7–16.7 < 0.01* Sleeping under tree Yes 244 147 (60.3) 5.2 2.2–12.3 < 0.01* No 110 32 (29.1) 1.0 –– Open sewage nearby house Yes 54 37 (67.5) 2.5 0.9–6.9 0.06 No 300 142 (47.3) 1.0 –– Irrigation nearby house Yes 93 84 (90.3) 8.1 1.9–12.4 < 0.01* No 261 95 (36.4) 1.0 –– Traveled to CL endemic areas Yes 54 46 (85.2) 13.9 4.4–14.3 <0.01* No 300 133 (44.3) 1.000 –– Own dogs and other animals Yes 248 137 (55.2) 2.272 1.0–5.1 0.04* No 106 42 (39.6) 1.000 –– n number, % per cent, Pos positive, AOR adjusted odds ratio, CI confidence interval *Significant at p < 0.05 Eshetu and Mamo Tropical Medicine and Health (2020) 48:39 Page 9 of 10

Conclusion Author details 1 In the study area, CL prevalence was progressively in- Department of Zoological Sciences, College of Natural and Computational Sciences, Addis Ababa University, PO Box 1176, Addis Ababa, Ethiopia. creasing within the past six and half year. Moreover, the 2Department of Microbial, Cellular and Molecular Biology, College of Natural study demonstrated that CL remained endemic in Dessie and Computational Sciences, Addis Ababa University, PO Box 1176, Addis town and its surroundings without being well docu- Ababa, Ethiopia. mented in the literature. Common CL risk factors in- Received: 12 March 2020 Accepted: 25 May 2020 criminated elsewhere are prevalent in the study area. The study revealed that the community lacked awareness about the meaning, transmission, and associated References risk factors of CL. To better control and monitor CL, 1. Handman E. Cell biology of leishmania. Adv Parasitol. 1999;44:1–39. awareness creation is necessary. The hospital lacked or- 2. Claborn DM. The biology and control of leishmaniasis vectors. J Infect Dis. ganized documentation system about CL patients and 2010;2(2):127–34. 3. WHO. Clinical forms of leishmaniasis. Available at: https://www.who.int/ requires improvement particularly in the specific diag- leishmaniasis/disease/clinical_forms_leishmaniases/en/index2.html, retrieved nostics ordered for a particular patient, drugs prescribed, 18 Dec 2019. and treatment outcomes as well as detailed clinical fea- 4. Marsden PD. Mucosal leishmaniasis (“espundia” Escomel, 1911). Trans R Soc Trop Med Hyg. 1986;80(6):859–76. tures, for instance, the duration of the lesions including 5. Kumari S, Ram VJ. Visceral Leishmaniasis: Clinical features, pathology, whether dry, wet, painful, or painless. Comprehensive diagnosis and chemotherapeutic developments. Drug News Perspect. 2002; future studies on the epidemiology and public health 15(7):417–31. 6. WHO. Essential leishmaniasis maps. Available at: [https://www.who.int/ burden of the disease in the area are essential. leishmaniasis/leishmaniasis_maps/en/], retrieved 27 Nov 2019. 7. WHO. Leishmaniasis fact sheet. Available at: [https://www.who.int/news- Abbreviations room/fact-sheets/detail/leishmaniasis], retrieved 27 Nov 2019. AOR: Adjusted odds ratio; AIDS: Acquired immunodeficiency syndrome; 8. CDC. Neglected tropical diseases. Available at: [https://www.cdc.gov/ BMH: Boru Meda Hospital; CI: Confidence interval; CL: Cutaneous globalhealth/ntd/diseases/index.html], retrieved 27 Nov 2019. leishmaniasis; CNS-IRB: College of Natural and Computational Sciences 9. Pires M, Wright B, Kaye PM, da Conceição V, Churchill RC. The impact of Institutional Review Board; FNAC: Fine needle aspiration cytology; leishmaniasis on mental health and psychosocial well-being: a systematic LCL: Localized cutaneous leishmaniasis; DCL: Diffuse cutaneous leishmaniasis; review. PLoS ONE. 2019;14(10):e0223313. NTDs: Neglected tropical diseases; OR: Odds ratio; VL: Visceral leishmaniasis; 10. Yanik M, Gurel MS, Simsek Z, Kati M. The psychological impact of cutaneous MCL: Mucocutaneous leishmaniasis; PKADL: Post-kala-azar dermal leishmaniasis. Clin Exp Dermatol. 2004;29:464–7. leishmaniasis; SIM: Sudan Interior Mission; SPSS: Statistical Package for Social 11. Alvar J, Yactayo S, Bern C. Leishmaniasis and poverty. Trends Parasitol. 2006; Sciences; WHO: World Health Organization 22(12):552–7. 12. Short EE, Caminade C, Thomas BN. Climate change contribution to the Acknowledgements emergence or reemergence of parasitic diseases. Infect Dis: Res Treat. 2017; The study received financial support from the Office of Academic Vice 10:1–7. President through the Department of Zoological Sciences, College of Natural 13. Ponte-Sucre A, Gamarro F, Dujardin J-C, Barrett MP, Lopez-Vélez R, Garcı́a- and Computational Sciences, Addis Ababa University. The authors would like Hernández R, Pountain AW, Mwenechanya R, Papadopoulou B. Drug to thank BMH staff for their kind support during data extraction. resistance and treatment failure in leishmaniasis: a 21st century challenge. PLoS Negl Trop Dis. 2017;11(12):e0006052. Authors’ contributions 14. Ozaras R, Leblebicioglu H, Sunbul FT, Balkan II, Yemisen M, Sencan I, Ozturk BE and HM conceived the research idea and participated in the design of R. The Syrian conflict and infectious diseases. Expert Rev Anti Infect Ther. the study. BE acquired the data and analyzed it. BE drafted the manuscript. 2016;14:547–55. HM critically revised the manuscript and finalized it. Both authors have read 15. Raad II, Chaftari A-M, Dib RW, Graviss EA, Hachem R. Emerging outbreaks and approved the final version of the manuscript. associated with conflict and failing healthcare systems in the Middle East. Infect Control Hosp Epidemiol. 2018;39:1230–6. ˜ Funding 16. Alvar J, Aparicio P, Aseffa A, Den Boer M. Can avate C, Dedet J-P, Gradoni L, This study had no specific funding. Horst RT, Lo´pez-Ve´lez R, Moreno J. The relationship between leishmaniasis and AIDS: the second 10 years. Clin Microbiol Rev. 2008;21(20893):334–59. 17. Oumeish OY. Cutaneous leishmaniasis: a historical perspective. Clin Availability of data and materials Dermatol. 1999;17:249–54. All data generated or analyzed during this study are included in this 18. Ashford RW, Bray MA, Hutchinson MP, Bray RS. The epidemiology of published article. cutaneous leishmaniasis in Ethiopia. Trans R Soc Trop Med Hyg. 1973;67(4): 568–601. Ethics approval and consent to participate 19. Lemma A, Foster WA, Gemechu T, Presonton PM, Bryceson A, Minter DM. The study was ethically approved by the College of Natural and Studies on leishmaniasis in Ethiopia. I. Preliminary investigations into the Computational Sciences Institutional Review Board (CNS-IRB), Addis Ababa epidemiology of cutaneous leishmaniasis in the highlands. Ann Trop Med University. Ethical approval was also granted from BMH. Informed consent Parasitol. 1969;63:455–72. ≥ was obtained from adult ( 18) participants and an assent from parents for 20. Wilkins HA. Studies on leishmaniasis in Ethiopia. VI. Incidence rates of the minors during the interview. Any information concerning the cutaneous leishmaniasis at Meta Abo. Ann Trop Med Parasitol. 1972;66(4): participants was kept confidential and the data analyzed only for the 457–66. intended purpose. 21. Padovese V, Terranova M, Toma L, Barnabas GA, Morrone A. Cutaneous and mucocutaneous leishmaniasis in Tigray, northern Ethiopia: clinical aspects Consent for publication and therapeutic concerns. Trans R Soc Trop Med Hyg. 2009;103(7):707–11. Not applicable. 22. Morrone A, Pitidis A, Pajno MC, Dassoni F, Latini O, Barnabas GA, Padovese V. Epidemiological and geographical aspects of leishmaniasis in Tigray, Competing interests northern Ethiopia: a retrospective analysis of medical records, 2005-2008. The authors declare that they have no competing interests. Trans R Soc Trop Med Hyg. 2011;105(5):273–80. Eshetu and Mamo Tropical Medicine and Health (2020) 48:39 Page 10 of 10

23. Bsrat A, Berhe N, Balkew M, Yohannes M, Teklu T, Gadisa E, Medhin G, Abera https://doi.org/10.1016/B978-0-323-55512-8.00104-6, Pp 776-798, ISBN 978-0- A. Epidemiological study of cutaneous leishmaniasis in Saesie Tsaeda-emba 323-55512-8. Elsevier. district, eastern Tigray, northern Ethiopia. Parasit Vector. 2015;8:149. 46. Seid A, Gadisa E, Tsegaw T, Abera A, Teshome A, Mulugeta A, Herrero M, 24. Yohannes M, Abebe Z, Boelee E. Prevalence and environmental Argaw D, Jorge A, Kebede A, Aseffa A. Risk map for cutaneous leishmaniasis determinants of cutaneous leishmaniasis in rural communities in Tigray, in Ethiopia based on environmental factors as revealed by geographical northern Ethiopia. PLoS Negl Trop Dis. 2019;13(9):e0007722. information systems and statistics. Geospatial Health. 2014;8(2):377–87. 25. Tamiru HF, Mashalla YJ, Mohammed R, Tshweneagae GT. Cutaneous 47. Desjeuxe P. The increase in risk factors for leishmaniasis worldwide. Trans leishmaniasis a neglected tropical disease: community knowledge, attitude Roy Soc Trop Med Hyg. 2001;95:239–43. and practices in an endemic area. Northwest Ethiopia. BMC Infect Dis. 2019; 48. Stewart CC, Brieger WR. Community views on cutaneous leishmaniasis in 19:855. Istalif, Afghanistan: implications for treatment and prevention. Int Q 26. Beyene HB, Alemu M, Degife M. Prevalence and clinical features of Community Health Educ. 2009;29(2):123–42. cutaneous leishmaniasis in Dembidolo District, Western Ethiopia: a cross- 49. Bern CL, Courtenay O, Alvar J. Cattle, sand flies and men: a systemic review sectional study. Int J Infect Trop Dis. 2015;2(1):31–8. of risk factor analysis in South Asia Leishmaniasis and implications for 27. Negera E, Gadisa E, Yamuah L, Engers H, Hussein J, Kuru T, Hailu A, Gedamu elimination. PLoS Negl Trop Dis. 2010;4:e599. L, Aseffa A. Outbreak of cutaneous leishmaniasis in Silti woreda, Ethiopia: 50. Dujardin J-C. Risk factors in the spread of leishmaniasis: towards integrated risk factor assessment and causative agent. Trans Roy Soc Trop Med Hyg. monitoring? Trends Parasitol. 2000;22(1):4–6. 2008;102:883–90. 51. Votýpka J1, Kasap OE, Volf P, Kodym P, Alten B. Risk factors for cutaneous 28. Lindtjorn B. Cutaneous leishmaniasis in the Sidamo highlands. Ethiop Med J. leishmaniasis in Cukurova region, Turkey. Trans R Soc Trop Med Hyg. 2012; 1981;25:211–22. 106:186-90. 29. Mengistu G, Humber DP, Ersumo M, Mamo T. High prevalence of elephantiasis and cutaneous leishmaniasis in Ocholo, south-west Ethiopia. Publisher’sNote Ethiop Med J. 1987;25(4):203–7. Springer Nature remains neutral with regard to jurisdictional claims in 30. Mengistu G, Laskay T, Gemetchu T, Humber D, Ersamo M, Evans D, published maps and institutional affiliations. Teferedegn H, Phelouzat MA, Frommel D. Cutaneous leishmaniasis in south- western Ethiopia: Ocholo revisited. Trans R Soc Trop Med Hyg. 1992;86(2): 149–53. 31. Pareyn M, Van den Bosch E, Girma N, van Houtte N, Van Dongen S, van der Auwera G, Massebo F, Shibru S, Leirs H. Ecology and seasonality of sandflies and potential reservoirs of cutaneous leishmaniasis in Ochollo, a hotspot in southern Ethiopia. PLoS Negl Trop Dis. 2019;13(8):e0007667. 32. Lemma W, Erenso G, Gadisa E, Balkew M, Gebre-Michael T, Hailu A. A zoonotic focus of cutaneous leishmaniasis in Addis Ababa. Ethiopia. Parasit Vector. 2009;2:60. 33. Bekele S, Bekele Y, Mulatu F, Lemma T, Tilahun H, Bizuneh E, Negussie S, Yamuah L, Wassie L, Abebeb M, Aseffa A. Recent trends of cutaneous leishmaniasis in Alert hospital, Addis Ababa. Ethiop Med J Supp1. 2014;37- 41. 34. Seife T, Benecha AK, Zewdu FT, Ayal A, Misganaw M. Treatment patterns and effectivness of anti-leishmaniasis agents for patients with cutaneous leishmaniasis at Boru Meda Hospital, South Wollo, North East Ethiopia, 2017/18. J Clin Exp Dermatol Res. 2018;9:3. 35. van Henten S, Adriaensen W, Fikre H, Akuffo H, Diro E, Hailu A. GV Auwer, van Griensven J. Cutaneous leishmaniasis due to Leishmania aethiopica. E Clinical Medicine. 2018;6:69–81. 36. Hailu A. Di MuccioT, Abebe T, Hunegnaw M, Kager PA. Gramiccia M. Isolation of Leishmania tropica from an Ethiopian cutaneous leishmaniasis patient. Trans Roy Soc Trop Med Hyg. 2006;100:53–8. 37. Assefa A. Leishmaniasis in Ethiopia: a systematic review and meta-analysis of prevalence in animals and humans. Heliyon. 2018;4:e00723. 38. Salam N, Al-Shaqha WM, Azzi A. Leishmaniasis in the Middle East: incidence and epidemiology. PLoS Negl Trop Dis. 2014;8(10):e3208. 39. Yadon ZE, Rodrigues LC, Davies CR. Indoor and peri-domestic transmission of American cutaneous leishmaniasis in Northwestern Argentina: a retrospective case-control study. Am J Trop Med Hyg. 2013;68(5):519–26. 40. Oryan A, Akbari M. A review of worldwide risk factors on leishmaniasis. Asian Pacific J Trop Med. 2016;10:925–32. 41. Reithinger RI, Mohsen M. Leslie. Risk factors of anthroponotic cutaneous leishmaniasis at the household level in Kabul, Afghanistan. PLoS Negl Trop Dis. 2010;4:e639. 42. Lockard RD, Wilson ME, Rodríguez NE. Sex-related differences in immune response and symptomatic manifestations to infection with Leishmania species. J Immunol Res. 2019:4103819. https://doi.org/10.1155/2019/ 4103819. 43. Ingersoll MA. Sex differences shape the response to infectious diseases. PLoS Pathog. 2017;13(12):e1006688. 44. Travi BL. OsorioY, Melby PC, Chandrasekar B, Arteaga L, Saravia NG. Gender is a major determinant of the clinical evolution and immune response in hamsters infected with Leishmania spp. Infect Immun. 2002;70(50019-9567): 2288–96. 45. Aronson NE, Magill AJ. Leishmaniasis. In: Hunter’s tropical medicine and emerging infectious diseases 10th ed (Ryan ET, Hill DR, ...Endy TP (eds); 2020.